Shuxuening Injection for the Prevention of Cerebral Vasospasm in Patients With Aneurysmal Subarachnoid Hemorrhage(SXN-CVS)

Sponsor

Xiaolin Chen, MD (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06138353

Collaborator

(none)

Enrollment

Arms

24.6

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Aneurysmal subarachnoid hemorrhage (SAH) is a frequent worldwide cause for stroke with a mortality of around 30%. Worldwide, almost 500 000 patients have aneurysmal SAH annually.An incidence of 2-16 cases of spontaneous SAH per 100 000 person-years was reported in a recent meta-analysis .

Surgical treatment of aneurysms is essential in the acute phase of aSAH patients, either by surgical clipping or by endovascular embolization. Although there are many factors that influence the prognosis of patients with aSAH, cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) are the main factors contributing to the high mortality rate (30-40% within 30 days) and poor long-term functional prognosis of patients after aSAH. Cerebral vasospasm (CVS) is defined as focal or diffuse temporary narrowing of vessel diameter due to contraction of smooth muscle in the arterial wall, which can be detected by digital subtraction angiography (DSA), transcranial ultrasound Doppler (TCD), magnetic resonance (MR), and CT angiography (CTA) or visualised during intraoperative.The prevalence of CVS after aSAH is 67% , with symptomatic patients (symptomatic vasospasm) in 30-40% of them and leading to ischaemic events in 10-45% of patients. It usually begins 3-4 days after bleeding, peaks at 7-10 days and finally resolves at around 14-21 days.

There is no effective treatment to prevent cerebral vasospasm events.Shuxuening Injection is a sterilized aqueous solution made by extraction of Ginkgo biloba. The study aims to clarify the clinical study of the efficacy and safety of Shuxuening Injection (10ml/branch) for the prophylactic of cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage.

Condition or Disease	Intervention/Treatment	Phase
Subarachnoid Hemorrhage, Aneurysmal	Drug: Shuxuening injection or placebo	Phase 2/Phase 3

Detailed Description

This was a randomized, double-blind, placebo-parallel controlled clinical trial.

Patients were randomly divided into 2 groups according to 1:1. Group1: Shuxuening injection treatment group (N1=25): Shuxuening injection (specification: 10ml/branch, Lonch Group Wanrong Pharmaceutical Co., Ltd.), 20 ml (2 branches) + 5% dextrose injection 250 ml, intravenously, once a day, from the first day of postoperative, treatment for 1 course of treatment, a total of 10-14 days; Group2: Placebo control group (N2=25): Shuxuening injection simulant (0.9% sodium chloride injection, specification: 10ml/cartridge, Kunming Yusi Pharmaceutical Co., Ltd.), 20 ml (2 cartridges) + 5% dextrose injection 250 ml, intravenously once a day, from the first day of postoperative, treatment for 1 course of treatment, for a total of 10-14 days; both groups received the basal treatment.

Basic treatment included nimodipine (oral nimodipine, 60 mg, 4 hours/dose), oxygen inhalation,blood pressure and cardiac monitoring, fluid balance and blood glucose management, etc., in accordance with the "2023 American Heart Association/American Stroke Association (AHA/ASA) Guidelines for the Management of Patients with Aneurysmal Subarachnoid Haemorrhage". Patients will be classified according to the Hunt-Hess grade, with H-H I-II grade placed in the general ward and III-V grade placed in the intensive care unit(ICU).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Shuxuening injection treatment : Shuxuening injection (specification: 10ml/branch, Lanzhi Group Wanrong Pharmaceutical Co., Ltd.), 20 ml (2 branches) + 5% dextrose injection 250 ml, intravenously, once a day, from the first day of postoperative aSAH, treatment for 1 course of treatment, a total of 10-14 days.Shuxuening injection treatment : Shuxuening injection (specification: 10ml/branch, Lanzhi Group Wanrong Pharmaceutical Co., Ltd.), 20 ml (2 branches) + 5% dextrose injection 250 ml, intravenously, once a day, from the first day of postoperative aSAH, treatment for 1 course of treatment, a total of 10-14 days.

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

To ensure blinding, personnel involved in randomisation coding or with potential access to the blind base, doctors or nurses administering the medication, should not be involved in activities such as selection of subjects, evaluation of efficacy, and assessment of safety, so as not to introduce bias. In addition, to ensure blinding, the packaging and batch numbers of the drugs in both groups will be identical, and the packaging batch numbers will be uniformly labelled. Each box will be labelled with a unique drug ID number. This number will be used to designate the treatment received by the patient, but will not indicate treatment assignment to the investigator or the patient.

Primary Purpose:

Treatment

Official Title:

Shuxuening Injection for the Prevention of Cerebral Vasospasm in Patients With Aneurysmal Subarachnoid Hemorrhage -- A Randomized, Double-blind, Placebo-parallel Controlled Clinical Trial

Anticipated Study Start Date :

Nov 13, 2023

Anticipated Primary Completion Date :

Nov 30, 2025

Anticipated Study Completion Date :

Nov 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Shuxuening injection treatment group Group1: Shuxuening injection treatment group (N1=25): Shuxuening injection (specification: 10ml/branch, Lanzhi Group Wanrong Pharmaceutical Co., Ltd.), 20 ml (2 branches) + 5% dextrose injection 250 ml, intravenously, once a day, from the first day of postoperative, treatment for 1 course of treatment, a total of 10-14 days.	Drug: Shuxuening injection or placebo Shuxuening injection treatment group : Shuxuening injection (specification: 10ml/branch, Lanzhi Group Wanrong Pharmaceutical Co., Ltd.), 20 ml (2 branches) + 5% dextrose injection 250 ml, intravenously, once a day, from the first day of postoperative, treatment for 1 course of treatment, a total of 10-14 days.
Placebo Comparator: Placebo control group Group2: Placebo control group (N2=25): Shuxuening injection simulant (0.9% sodium chloride injection, specification: 10 ml/cartridge, Kunming Yusi Pharmaceutical Co., Ltd.), 20 ml (2 cartridges) + 5% dextrose injection 250 ml, intravenously dripped once a day, from the first day of postoperative, treatment for 1 course of treatment, for a total of 10-14 days.	Drug: Shuxuening injection or placebo Shuxuening injection treatment group : Shuxuening injection (specification: 10ml/branch, Lanzhi Group Wanrong Pharmaceutical Co., Ltd.), 20 ml (2 branches) + 5% dextrose injection 250 ml, intravenously, once a day, from the first day of postoperative, treatment for 1 course of treatment, a total of 10-14 days.

Arm

Intervention/Treatment

Experimental: Shuxuening injection treatment group

Group1: Shuxuening injection treatment group (N1=25): Shuxuening injection (specification: 10ml/branch, Lanzhi Group Wanrong Pharmaceutical Co., Ltd.), 20 ml (2 branches) + 5% dextrose injection 250 ml, intravenously, once a day, from the first day of postoperative, treatment for 1 course of treatment, a total of 10-14 days.

Drug: Shuxuening injection or placebo

Shuxuening injection treatment group : Shuxuening injection (specification: 10ml/branch, Lanzhi Group Wanrong Pharmaceutical Co., Ltd.), 20 ml (2 branches) + 5% dextrose injection 250 ml, intravenously, once a day, from the first day of postoperative, treatment for 1 course of treatment, a total of 10-14 days.

Placebo Comparator: Placebo control group

Group2: Placebo control group (N2=25): Shuxuening injection simulant (0.9% sodium chloride injection, specification: 10 ml/cartridge, Kunming Yusi Pharmaceutical Co., Ltd.), 20 ml (2 cartridges) + 5% dextrose injection 250 ml, intravenously dripped once a day, from the first day of postoperative, treatment for 1 course of treatment, for a total of 10-14 days.

Drug: Shuxuening injection or placebo

Outcome Measures

Primary Outcome Measures

Number of Participants with cerebral vasospasm(CVS) [Cerebral vasospasm events within 14 days]
The prevalence of CVS after aSAH is 67% , with symptomatic patients (symptomatic vasospasm) in 30-40% of them and leading to ischemic events in 10-45% of patients. It usually begins 3-4 days after rupture bleeding, peaks at 7-10 days and finally resolves at around 14-21 days.

Secondary Outcome Measures

Rate of Delayed Cerebral Ischemic(DCI) [Delayed cerebral ischemic events within 14 days]
Delayed cerebral ischemic events within 14 days

Other Outcome Measures

modified Rankin scale(mRS) [modified Rankin scale(mRS) within 14 days and 90 days]
modified Rankin scale(mRS) ranged from a minimum of 0 to a maximum of 5, with higher scores representing a worse outcome.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

adult patients (> 18 years of age)
patients who were diagnosed with aneurysmal subarachnoid hemorrhage
the aneurysms were treated by microsurgery clipping or endovascular coiling
Time from onset to surgery is less than or equal to 72 hours;
no new hemorrhage or new infarction on first postoperative CT;
signed informed consent.

Exclusion Criteria:

mRS >1 before onset
history of microsurgery clipping or endovascular coiling
anemia (hemoglobin <10g/dL), thrombocytopenia (platelet count <100×10^{9/L), or
leukopenia (white blood cell count <3×10}9/L) at randomization
patients with chronic liver and kidney dysfunction (including those with alanine aminotransferase (ALT) and aliquot aminotransferase (AST) > 3 times the upper limit of normal, and those with blood creatinine (Scr) > 2 times the upper limit of normal)
patients suffering from cardiorespiratory insufficiency disease such as heart failure, severe heart disease, respiratory failure
allergy to Shuxuening Injection
those who have used Shuxuening Injection before enrolled
patients with end-stage disease, those with a life expectancy of less than 3 months
women who are prepare for pregnancy in 3 months, pregnant or breastfeeding
those who are participating or have participated in other clinical trials within the past 1 month
patients are unable to comply with this study due to mental illness, cognitive or emotional disorders, etc. or that the investigator think patients inappropriate for this study